The Schwann cells (SC) are responsible of myelin production in peripheral nervous system. These cells wrap the axons and remain associated to protect them and allow the correct and efficient action potential transmission1,2. Unfortunately, hereditary and acquired demyelinating diseases of the peripheral nervous system (PNS) are numerous and affect an increasing number of people3.
Acquired demyelinating diseases are even more common as they include diabetic peripheral neuropathy4, drug-related peripheral demyelinating diseases, leprosy and peripheral demyelinating diseases of inflammatory etiology5. Demyelinating peripheral neuropathy is a major complication of diabetes and a cause of considerable morbidity6. This neuropathy is characterized by the loss and/or degeneration of neurons and Schwann cells, and the slowing of nerve conduction velocities7,8. Moreover, it has been reported that at least 50% of diabetic patients develop one or several forms of diabetic neuropathies within 25 years after diagnosis9.
In the PNS, hereditary demyelinating diseases are rare but remain among the most common hereditary diseases10. While they are rarely lethal, they range from life threatening to severely affecting life and therefore put a high burden on public health systems. The most common of these diseases are termed as Charcot-Marie-Tooth (CMT) diseases10. Numerous genes mutated in these diseases are known but the molecular mechanisms that they affect often remain unclear11.
The etiologies of all these acquired and hereditary peripheral diseases are diverse but they all result in demyelination. Thus an important challenge is to understand the cellular and molecular events that underlie myelination and demyelination. In this way, recent studies show that mitochondria dysfunctions are involved in an increasing number of demyelinating neurodegenerative diseases12,13. Myelin sheath mitochondria have been shown to be essential for neuron homeostasis14 but their morphological and physiological properties remain elusive. It is well known that patients suffering from mitochondrial multisystem disorders often show a peripheral neuropathy in addition to other more debilitating symptoms12,15. Myelinating Schwann cells (mSC) of patients suffering these diseases display features of demyelination as well as abnormal mitochondria. More directly, some acquired demyelinating PNS diseases appear to be linked to defects in mitochondrial functions. For example diabetes and the treatment with some drugs such as amiodarone, perhexiline, Tacrolimus have been linked with perturbation of mitochondrial functions and to mitochondrial stress. Consistently, one of the main side effect of these drugs and the main comorbidity associated with diabetes is demyelinating peripheral neuropathy16.